First Author | Chang X | Year | 2015 |
Journal | Proc Natl Acad Sci U S A | Volume | 112 |
Issue | 15 | Pages | E1888-97 |
PubMed ID | 25825742 | Mgi Jnum | J:220533 |
Mgi Id | MGI:5635311 | Doi | 10.1073/pnas.1422490112 |
Citation | Chang X, et al. (2015) RNA-binding protein hnRNPLL regulates mRNA splicing and stability during B-cell to plasma-cell differentiation. Proc Natl Acad Sci U S A 112(15):E1888-97 |
abstractText | Posttranscriptional regulation is a major mechanism to rewire transcriptomes during differentiation. Heterogeneous nuclear RNA-binding protein LL (hnRNPLL) is specifically induced in terminally differentiated lymphocytes, including effector T cells and plasma cells. To study the molecular functions of hnRNPLL at a genome-wide level, we identified hnRNPLL RNA targets and binding sites in plasma cells through integrated Photoactivatable-Ribonucleoside-Enhanced Cross-Linking and Immunoprecipitation (PAR-CLIP) and RNA sequencing. hnRNPLL preferentially recognizes CA dinucleotide-containing sequences in introns and 3' untranslated regions (UTRs), promotes exon inclusion or exclusion in a context-dependent manner, and stabilizes mRNA when associated with 3' UTRs. During differentiation of primary B cells to plasma cells, hnRNPLL mediates a genome-wide switch of RNA processing, resulting in loss of B-cell lymphoma 6 (Bcl6) expression and increased Ig production-both hallmarks of plasma-cell maturation. Our data identify previously unknown functions of hnRNPLL in B-cell to plasma-cell differentiation and demonstrate that the RNA-binding protein hnRNPLL has a critical role in tuning transcriptomes of terminally differentiating B lymphocytes. |